Synthesis and utilisation of biochemical tools to investigate fatty acid and lipid metabolism

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Synthesis a range of novel glycerol and fatty acid analogues/derivatives as tools to investigate fatty acid and lipid metabolism in fast dividing cells, i.e. parasites. These will be utilised to their uptake and utilisation in protozoan parasites and mammalian cell.The student will be undertaking various types of chemical synthesis of various natural product motifs, including making a range of lipid-like molecule and glycerol analogues as novel tools to investigate their metabolism to inform about general lipid metabolism.The student will investigate the uptake of and utilisation of glycerol and fatty acid analogues/derivatives, either as energy sources, or their incorporation into lipid membranes which may alter their biophysical properties, disrupting normally cell functions and processes. This includes fatty acid elongation, dehydrogenation, as well as beta-oxidation of fatty acids.The glycerol and fatty acid analogues/derivatives will also be utilised to explore structure activity relationships against specific enzymes, which have been previously validated as drug targets by the group for various protozoan parasites that cause neglected tropical diseases. The student will be fully trained at a Cat 3 level to undertake parasite and mammalian cell culture and biochemical manipulations. This will allow them to undertake EC50 value determinations and biochemical phenotyping. The student will subsequently synthesise and utilize novel affinity probes of their best hits, to ensure "on-target" and mode of action studies.